Prednisolone Disposition and Protein Binding in Oral Contraceptive Users*
- 1 April 1983
- journal article
- research article
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 56 (4) , 702-709
- https://doi.org/10.1210/jcem-56-4-702
Abstract
Combined estrogen-progestogen oral contraceptives (OC) have been shown to alter the metabolism of certain drugs, including corticosteroids, as well as affect circulating protein concentrations. To assess these effects with regard to prednisolone, the pharmacokinetics and protein binding of this steroid were evaluated in eight female OC users and compared with results from eight male and five female non-OC users. All volunteers received 40 mg prednisolone, iv, and steroid concentrations were measured by high pressure liquid chromatography. Plasma clearance of total prednisolone in females on OC was 96 ± 9 (SD) ml/min·1.73 m2, significantly (P < 0.001) lower than those in both male and female controls (205 ± 46 and 187 ± 22 ml/min·1.73 m2). The prednisolone half-life and mean residence time were longer, while the steady state volume of distribution was smaller for OC users. Unbound prednisolone was measured by equilibrium dialysis, and pharmacokinetic and protein binding parameters were calculated from free prednisolone concentrations. A significantly higher (2-fold) concentration of transcortin was found in OC users. Evaluation of free prednisolone parameters showed a significantly lower clearance and decreased volume of distribution, without alteration of the mean residence time for the OC users. Dual OC effects on binding and elimination of prednisolone occur with the net result of a 2-fold increase in the area under the free concentration-time curve, indicative of a marked reduction in the biotransformation rate of the steroid. (J Clin Endocrinol Metab56: 702, 1983)Keywords
This publication has 13 references indexed in Scilit:
- Changes in plasma drug binding and α1-acid glycoprotein in mother and newborn infantClinical Pharmacology & Therapeutics, 1981
- Serum protein binding of prednisolone in four speciesJournal of Pharmaceutical Sciences, 1980
- CHARACTERIZATION OF CHOLESTASIS INDUCED BY ESTRADIOL-17 BETA-D-GLUCURONIDE IN THE RAT1980
- IMPAIRED ELIMINATION OF CAFFEINE BY ORAL-CONTRACEPTIVE STEROIDS1980
- Disposition of chlordiazepoxide: Sex differences and effects of oral contraceptivesClinical Pharmacology & Therapeutics, 1979
- Corticosteroid analysis in biological fluids by high-performance liquid chromatographyJournal of Chromatography B: Biomedical Sciences and Applications, 1979
- A comparison of numerical integrating algorithms by trapezoidal, Lagrange, and spline approximationJournal of Pharmacokinetics and Biopharmaceutics, 1978
- A statistical method for the estimation of binding parameters in a complex systemAnalytical Biochemistry, 1976
- Potentiation of the Biologic Effect of Administered Cortisol by Estrogen TreatmentJournal of Clinical Endocrinology & Metabolism, 1963
- THE EFFECT OF ESTROGEN ADMINISTRATION ON THE METABOLISM AND PROTEIN BINDING OF HYDROCORTISONEJournal of Clinical Endocrinology & Metabolism, 1960